MAXILLOFACIAL SURGERY

Original Articles EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUS-

ITIS: A PILOT STUDY
Daniela Miricescu1a, Alexandra Totan1b*, Ioana Ruxandra Rusu2c, Vitali Movradin3d, Mihaela Moisescu4e,
Constatin Ștefani5f, Iulia-Ioana Stănescu1g, Radu Rădulescu1h, Cosmin Totan6i, George Costin Rusu7j,
Maria Greabu1k
1.
Department of Biochemistry, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
2.
Department of Anatomy and Embryology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
3. Private Dental Practice, Bucharest
4.
Center for Excellence in Biophysics and Cellular Biotechnology Research, “Carol Davila” University of Medicine and Pharmacy
5.
Department of Family Medicine, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, “Carol Davila” University
Central Emergency Military Hospital, Bucharest, Romania
6.
Department of Oral Maxillofacial Surgery, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania
7.
Department of Modern Languages, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest, Romania

a
Chem, MSc, PhD, Lecturer
b
DMD, PhD, Associate Professor
c
DMD, PhD, Lecturer
d
DMD
e
DMD, PhD, Lecturer
f
DMD, PhD, Lecturer
g
DMD, PhD, Assistant Professor
h
DMD, PhD, Assistant Professor
i
DMD, PhD, Lecturer
j
DMD, PhD, Lecturer
k
DMD, PhD, Professor, Head

ABSTRACT DOI: https://doi.org/10.25241/stomaeduj.2019.6(2).art.4

OPEN ACCESS This is an Open Access
article under the CC BY-NC 4.0 license.
Introduction: Chronic odontogenic maxillary sinusitis (CMOS) is a frequent
inflammatory process pertaining to the oro-maxilo-facial pathology. Platelet-rich Peer-Reviewed Article

plasma (PRP) is a natural source of growth factors, which have the potential to Citation: Miricescu D, Totan A, Rusu IR,
Movradin V, Moisescu M, Ștefani C, Stănescu I I,
stimulate and accelerate the wound healing process. Rădulescu R, Totan C, Rusu GC, Greabu M, Effects of
The aim of this study is to observe the effects of the PRP growth factors in patients etching mode on bond strength of universal
adhesives. Stoma Edu J. 2019;6(2):118-123
with CMOS.
Received: June 11, 2019
Methodology: Inflammatory oral mucosa was collected from five patients Revised: June 21, 2019
diagnosed with CMOS, and it was incubated with 2 mL PRP for 7 days. PRP Accepted: June 26, 2019
Published: June 27, 2019
was obtained from venous blood collection from each patient. The control
*Corresponding author:
samples were represented by inflammatory sinus mucosa without adding PRP. Associate Professor Alexandra Totan, DMD, PhD
The following biomarkers were measured using cell lysate: insulin receptor (IR) Department of Biochemistry, Faculty of Dental
Medicine, “Carol Davila” University of Medicine a
and insulin-like growth factor 1 receptor (IGF-1R), glycogen synthase kinase 3 nd Pharmacy Bucharest, Bucharest, Romania
8, Blvd. Eroii Sanitari, Sector 5,
beta (GSK3β), glycogen synthase kinase 3 alfa (GSK3α) performed by Multiplex RO-050474 Bucharest, Romania
technology. Tel: +40721274932;
Fax: +400213110984;
Results: The results revealed statistically increased levels for all four parameters e-mail: alexandratotan99@gmail.com

in patients with CMOS versus controls (p < 0.05). Growth factors from PRP bind Copyright: © 2019
to receptors with tyrosine kinase activity, cellular event being correlated with the Editorial Council for the Stomatology Edu
Journal.
cell proliferation. The radiological control of patients 10 months after PRP
administration revealed a decrease in the thickness of the sinus lining up to 3
times.
Conclusions: The growth factors released from platelets should be regarded as a
positive effect source in the case of patients diagnosed with CMOS. These growth
factors should activate the oligopotente stem cells which will finally lead to sinus
mucosa regeneration. Future studies are needed to understand the molecular
mechanisms that occur at the sinus level.
Keywords: Inflammation; Platelet-rich plasma (PRP); Sinusitis; Chronic
odontogenic maxillary sinusitis (CMOS).

118 Stoma Edu J. 2019;6(2): 118-123 http://www.stomaeduj.com

 EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY
1. Introduction
CMOS is an inflammation of the maxillary sinus
caused by dental infection. Patients with chronic
periodontitis have an increased risk of developing
maxillary sinusitis caused by intra-antral foreign
bodies or by oroantral fistulas after tooth extraction
[1,2]. According to the literature in the field, the
incidence of this disease in the adult population
is 10-12%, but according to the latest studies, the
incidence increased to 41% [3-5]. So far, there is
no gold standard in choosing the most suitable
treatment method for this inflammatory process.
Until now, specialized literature suggests 3 main
clinical methods to treat CMOS: the Caldwell-Luc
operation, functional endoscopic sinus surgery
and finally dental extraction or dental treatment.
Using these surgical methods presents several
disadvantages: bleeding, infraorbital nerve damage,
facial swelling, pain, and significant hemorrhage may
appear. These treatment methods require patient
hospitalization and general anesthesia with possible
complications [6,7]. Platelet-rich-plasma (PRP) is a
natural source of growth factors being considered an
endogenous therapeutic technology used in many
medical fields. PRP has the potential to stimulate and
accelerate the healing process [8,9,14]. The main aim
of this pilot study was to observe the effects of PRP-
related growth factors in patients diagnosed with
CMOS.
2. Materials and Methods
The pilot study included five patients (4 men and 1
woman aged 40-64) diagnosed with CMOS following
a dental exam and computer tomography (CT)
(Fig.1). PRP was obtained by venous blood collection
in tubes containing separating gel with an inert
polymer necessary to ensure the separation between
a b
Figure 1. Computer tomography from a patient included in the study:
a. Coronal CT dental scan showing. Opacified right maxillary sinus - before PRP treatment;
b. Opacity of right maxillary sinus reduced after PRP intrasinusal infiltration (Used with permission of pacient) - after PRP treatment
Stomatology Edu Journal
Original Articles
erythrocytes and platelers. Sodium citrate was used
as anticoagulant to prevent the initiation of the
coagulation cascade. The samples were centrifuged
at 4000 rpm for 5 minutes. Using the trepanation
technique, inflammatory sinus mucosa was collected
from the maxillary sinus in sterile tubes and was
incubated with PRP for 7 days. PRP was injected in the
inflammatory maxillary sinus PRP was injected in all
patients based on a clinical chart.
Along with the clinical study, lab study was conducted
in order to underline the PRP procedure on the
mucus, to prove the effect of growth factors implied
in the local healing process. The control samples were
represented by the inflammatory mucosa that were
not treated with PRP and were collected in sterile
tubes containing phosphate-buffered aline solution
(pH 7.2). The samples were sonicated on ice (10 min,
Sonoplus HD 2070, BANDELIN electronic GmbH &
Co. KG, Berlin, Germany) and the lysate was stored at
-80°C. All patients signed an informed consent and
agreed to participate in the study. Insulin receptor (IR),
insulin-like growth factor 1 receptor (IGF-1R) glycogen
synthase kinase 3 beta (GSK3β) and glycogen synthase
kinase 3 alfa (GSK3α) were detected using Luminex
technology and Magnetic Bead-Based Multiplex assays
(Akt/mTOR, Total protein 11-plex Magnetic Bead kit, 96
well plate, 48-612 MAG). This method can detect all the
mentioned biomarkers from the same sample.
2.1. Statistical analysis
The statistical analysis was performed using student
t-test and p-value less then 0.05 was considered
statistically significant.
3. Results
The results of our study reveled statistically increased
levels of IR, IGF-1, GSK3β and GSK3α for mucosa
samples treated with PRP compared with mucosa
119
 EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY
Original Articles Table 1. Mean values for all four parameters detected.
Parameters (MFI)
IGF-1R
IR
GSK3β
GSK3α
Figure 2. Graphic represenation of all 4 studied parameters versus their controls
samples that did not received PRP. Our results are
presented in Table 1 and Fig. 2.
4. Discussions
PRP is currently used in many medical fields such
as orthopedic, pediatric, maxillofacial and plastic
surgery, sport medicine, and cosmetic and dental
implant surgery [9-13]. FDA (Food and Drug
Administration) has classified PRP as a minimally
manipulated tissue and an autologous blood product
with multiple benefits for patients [14]. Growth
factors play key roles in the complex process of tissue
healing and regeneration, being signaling proteins
that influence the metabolism of other cells [15,16].
Transforming growth factor (TGF-β), platelet-derived
growth factor (PDGF), vascular endothelial growth
factor (VEGF), insulin-like growth factor-1 (IGF-1) and
epidermal growth factor (EGF) are present in PRP
[10-16]. PDGF is secreted by platelets, macrophages,
keratinocytes, endothelial and muscle cells. PDGF
is one of the growth factors that are secreted when
an injury occurs, stimulating many metabolic
processes such as protein and collagen synthesis.
It also promotes the proliferation and migration
of endothelial cells, exerting angiogenic effects,
stimulates the production of TGF-β that initiates
collagen synthesis and stimulates the production
120
Patients Controls p
142.33 ± 16.7 63.37 ± 16.7 < 0.05
204.5 ± 8.23 78.97 ± 8.23 < 0.05
70.625 ± 20.44 30 ± 20.44 < 0.05
111.75 ± 43.12 40.375 ± 43.12 < 0.05
of IGF-1. The positive effects of PDGF were seen
in the treatment of the ulcerous foot in diabetic
patients [17,18]. Platelets, macrophages, fibroblasts
and mesenchimal stem cells secrete EGF, which is
released at a high concentration at the beginning of
the healing process. EGF plays important roles in the
proliferation, differentiation, growth and migration
of keratinocytes and epithelial cells [14,15].
IGF is secreted by fibroblasts and is involved mainly
in the inflammatory and proliferative phase II, 58,
72. Decreased IGF concentrations were observed
in diabetic patients with chronic wounds. Clinical
trials conducted on laboratory animals such as
diabetic and healthy rats, or rabbits showed that the
exogenous IGF application accelerates the healing
process [16-18]. In combination with other growth
factors such as PDGF and EGF, IGF exhibits much more
powerful biological effects promoting keratinocyte
migration and enhancing tissue repair [19-21]. VEGF
is secreted by plateles, keratinocytes, macrophages
and fibroblasts and manifests strong paracrine
effects on endothelial cells, promotes and supports
the process of wound angiogenesis. It is the main
growth factor that initiates the angiogenesis process
in granulation tissue [21,22]. VEGF growth factors
are implicated in the physiological and pathological
processes of vasculogenesis, angiogenesis, vascular
Stoma Edu J. 2019;6(2): 118-123 http://www.stomaeduj.com
 EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY
permeability and lymhangiogenesis [22,23].
Clinical and experimental studies conducted on
diabetic mice and dogs, as well as diabetic patients
reported very good results by applying VEGF, which
accelerate healing by increasing epithelialization,
angiogenesis and granulation tissue formation [24-
27]. Many cell types secrete TGFβ such as platelets,
T lymphocytes, macrophages, keratinocytes,
fibroblasts, muscle and endothelial cells. TGFβ
induces synthesis of collagen and fibronectin due
to chemotactic effects on macrophages and inhibits
the activity of metalloproteases [25]. IGF-1R, IR,
GSK3α, GSK 3β, detected in our pilot study are part
of the signaling cascade called Akt/mTOR or protein
kinase B. This signaling pathway plays a central role in
numerous cellular processes such as cell proliferation
regulation, survival and glucose metabolism. Akt is
activated by insulin, which presents the receptor with
tyrosine kinase activity [28]. By binding the insulin
to the extracellular domain of the receptor there
occurs the autophosphorylation of the receptor
that is recognized by the IRS (insulin receptor
substrate), and further there is a series of cascade
phosphorylates with Akt activation that will lead to
cell growth and proliferation. Akt may be activated
by many growth factors such as those found in PRP
or cytokines [28]. The results of the current study
reflect statistically significant increased levels for IGF-
1R, IR, GSK3α, GSK3β in the case of PRP-treated oral
mucosa versus oral mucosa without PRP treatment.
Growth factors from PRP bind to receptors with
tyrosine kinase activity, such as the insulin receptor,
actives Akt signaling pathway, promotes increase
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Stomatology Edu Journal
Original Articles
in protein translation and cell growth. The results of
the biochemical evaluations are correlated with the
findings of CT performed at 10 months after the PRP
injection, according to Fig. 1.
5. Conclusions
In conclusion, the growth factors released from
platelets should be regarded as a positive effect
source in the case of patients diagnosed with
CMOS. These growth factors should activate the
oligopotent stem cells which will finally lead to sinus
mucosa regeneration. Future studies are needed to
understand the molecular mechanisms that occur at
the sinus level.
Author Contributions
All authors equally contributed to the present
manuscript. DM: participated in sample analysis
and manuscript writing; AT: participated in sample
analysis and manuscript writing, IRR: participated
in study design, data collection; VM: participated in
the study design and sample collection, being the
OMF surgeon to produce the clinical samples; MM:
participated in sample analysis, CS: participated
in manuscript writing; IIS: manuscript writing; RR:
manuscript writing; CT: participated in manuscript
writing; GCR: translation of the text, proposing and
managing the whole work; MG: participated in
critical review of the manuscript.
Acknowledgments
This work was proposed and managed by The
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Daniela MIRICESCU
Chem, MSc, PhD, Lecturer
Department of Biochemistry
Faculty of Dental Medicine
„Carol Davila” University of Medicine and Pharmacy Bucharest
Bucharest, Romania

CV
Daniela Miricescu graduated from the Faculty of Chemistry (Biochemistry Department) in 2006, in 2008 she obtained
her Master’s of Biochemistry and Molecular Biology (Biology Faculty) and in 2012 she obtained her PhD from the „Carol
Davila” University of Medicine and Pharmacy Bucharest, Romania.
Since 2016 she has been a lecturer at Department of Biochemistry, Faculty of Dental Medicine, „Carol Davila” University
of Medicine and Pharmacy Bucharest.
Her research field includes salivary studies on oxidative stress in various oral pathologies, the effects of obesity on
laboratory animals, the effects of PLGA nanoparticles both in vivo and in vitro, the effects of plasma-rich plasma in
patients diagnosed with chronic maxillary sinusitis, and the study of Akt (protein kinase B) signaling pathways in health
and disease .

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 EFFECT OF PLATELET-RICH PLASMA ON CHRONIC ODONTOGENIC MAXILLARY SINUSITIS: A PILOT STUDY

Original Articles
Questions
1. PRP is:
qa. Natural source of growth factors
qb. Natural source of proinflammatory agents
qc. Natural source of antiinflammatory agents
qd. Natural source of stem cells

2. PRP may be used in:

qa. Ortopedic surgery
qb. Dental implant surgery
qc. Plastic surgery
qd. Cosmetic

3. IGF:
qa. Is secreted by fibroblasts
qb. Is involved in proliferative phase
qc. Promotes keratinocytes migration
qd. Promotes tissue repair

4. Akt (protein kinase B) is implicated in:

qa. Cell proliferation
qb. Glucose metabolism
qc. Celular survival
qd. Necrosis

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